Summary of Work: We have developed primary rat and mouse cell strains from the transgenic Big Blue rat and mouse. Both cell strains are genetically stable and mostly diploid with low spontaneous mutation, SCE and micronuclei frequencies making them useful for molecular toxicology studies. In addition, we have studied the mutagenic consequence of defects in human mismatch repair (MMR) genes following treatment with DNA damaging agents. We have previously shown that cytotoxicity to methylmethane sulfonate (MMS) is mediated through MMR. Mutations may result in the absence of MMR processing of MMS damage. The spectra of mutations following MMS treatment of MMR-deficient and MMR-proficient cells stongly suggest that MMR may be involved in the repair of a - mismatch repair mutation rate hprt mutational spectra HHUA hMutS-alpha hMutS-beta 6-thioguanine